SYNTHESIS OF ETRAHYDROSPIRO[ISOBENZOFURAN-1(3H),2'-PYRAN]-3-ONE AND ETRAHYDROSPIRO[ISOBENZOFURAN-1(3H),2'-PYRAN]-3-ONE

The synthesis of novel aryl spiroketals, which contain a, similar subs titution pattern to that present in the antifungal agents the papulaca ndins, is described. Thus, spiroketal (7) was obtained from acid-catal ysed cyclization of the keto alcohol (13), and spiroketal (8) was obta ined from acid-catalysed cyclization of keto alcohols (12) and (19). K eto alcohols (12), (13) and (19) in turn were prepared by ortho-direct ed lithiation of amides (10), (11) and oxazoline (17) respectively, fo llowed by reaction with delta-valerolactone. Substitution of the aroma tic ring occurred at the sterically hindered position ortho to both th e methoxy and ortho-directing metalation group. In an alternative appr oach to the synthesis of the desired spiroketals, two palladium(0)-cat alysed coupling strategies were examined. The Stille coupling between the aryl stannane (24) and iodoglucal (25) resulted in a low yield of the aryl C-glycoside (21). Likewise, a low yield for the same coupled product (21) was achieved by a Suzuki coupling between the arylboronic acid (26) and iodoglucal (25).